TM6SF2 reduces lipid accumulation in vascular smooth muscle cells by inhibiting LOX-1 and CD36 expression.

TM6SF2, predominantly expressed in the liver and intestine, is closely associated with lipid metabolism. We have demonstrated the presence of TM6SF2 in VSMCs within human atherosclerotic plaques. Subsequent functional studies were conducted to investigate its role in lipid uptake and accumulation in human vascular smooth muscle cells (HAVSMCs) using siRNA knockdown and overexpression techniques. Our results showed that TM6SF2 reduced lipid accumulation in oxLDL-stimulated VSMCs, likely through the regulation of lectin-like oxLDL receptor 1 (LOX-1) and scavenger receptor cluster of differentiation 36 (CD36) expression. We concluded that TM6SF2 plays a role in HAVSMC lipid metabolism with opposing effects on cellular lipid droplet content by downregulation of LOX-1 and CD36 expression.

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Triggers Vascular Smooth Muscle Cell Senescence and Apoptosis: Implication of Its Direct Role in Degenerative Vascular Disease.

OBJECTIVE: PCSK9 (proprotein convertase subtilisin/kexin type 9) plays a critical role in cholesterol metabolism via the PCSK9-LDLR (low-density lipoprotein receptor) axis in the liver; however, evidence indicates that PCSK9 directly contributes to the pathogenesis of various diseases through mechanisms independent of its LDL-cholesterol regulation. The objective of this study was to determine how PCSK9 directly acts on vascular smooth muscle cells (SMCs), contributing to degenerative vascular disease. Approach and Results: We first examined the effects of PCSK9 on cultured human aortic SMCs. Overexpression of PCSK9 downregulated the expression of ApoER2 (apolipoprotein E receptor 2), a known target of PCSK9. Treatment with soluble recombinant human ApoER2 or the DNA synthesis inhibitor, hydroxyurea, inhibited PCSK9-induced polyploidization and other cellular responses of human SMCs. Treatment with antibodies against ApoER2 resulted in similar effects to those observed with PCSK9 overexpression. Inducible, SMC-specific knockout of Pcsk9 accelerated neointima formation in mouse carotid arteries and reduced age-related arterial stiffness. PCSK9 was expressed in SMCs of human atherosclerotic lesions and abundant in the "shoulder" regions of vulnerable atherosclerotic plaques. PCSK9 was also expressed in SMCs of abdominal aortic aneurysm, which was inversely related to the expression of smooth muscle α-actin. CONCLUSIONS: Our findings demonstrate that PCSK9 inhibits proliferation and induces polyploidization, senescence, and apoptosis, which may be relevant to various degenerative vascular diseases.

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Induction of ferroptosis promotes vascular smooth muscle cell phenotypic switching and aggravates neointimal hyperplasia in mice.

BACKGROUND: Stent implantation-induced neointima formation is a dominant culprit in coronary artery disease treatment failure after percutaneous coronary intervention. Ferroptosis, an iron-dependent regulated cell death, has been associated with various cardiovascular diseases. However, the effect of ferroptosis on neointima formation remains unclear. METHODS: The mouse common right carotid arteries were ligated for 16 or 30 days, and ligated tissues were collected for further analyses. Primary rat vascular smooth muscle cells (VSMCs) were isolated from the media of aortas of Sprague-Dawley (SD) rats and used for in vitro cell culture experiments. RESULTS: Ferroptosis was positively associated with neointima formation. In vivo, RAS-selective lethal 3 (RSL3), a ferroptosis activator, aggravated carotid artery ligation-induced neointima formation and promoted VSMC phenotypic conversion. In contrast, a ferroptosis inhibitor, ferrostatin-1 (Fer-1), showed the opposite effects in mice. In vitro, RSL3 promoted rat VSMC phenotypic switching from a contractile to a synthetic phenotype, evidenced by increased contractile markers (smooth muscle myosin heavy chain and calponin 1), and decreased synthetic marker osteopontin. The induction of ferroptosis by RSL3 was confirmed by the increased expression level of ferroptosis-associated gene prostaglandin-endoperoxide synthase 2 (Ptgs2). The effect of RSL3 on rat VSMC phenotypic switching was abolished by Fer-1. Moreover, N-acetyl-L-cysteine (NAC), the reactive oxygen species inhibitor, counteracted the effect of RSL3 on the phenotypic conversion of rat VSMCs. CONCLUSIONS: Ferroptosis induces VSMC phenotypic switching and accelerates ligation-induced neointimal hyperplasia in mice. Our findings suggest inhibition of ferroptosis as an attractive strategy for limiting vascular restenosis.

Antiatherosclerotic effect of dehydrocorydaline on ApoE-/- mice: inhibition of macrophage inflammation.

Despite improvements in cardiovascular disease (CVD) outcomes by cholesterol-lowering statin therapy, the high rate of CVD is still a great concern worldwide. Dehydrocorydaline (DHC) is an alkaloidal compound isolated from the traditional Chinese herb Corydalis yanhusuo. Emerging evidence shows that DHC has anti-inflammatory and antithrombotic benefits, but whether DHC exerts any antiatherosclerotic effects remains unclear. Our study revealed that intraperitoneal (i.p.) injection of DHC in apolipoprotein E-deficient (ApoE-/-) mice not only inhibited atherosclerosis development but also improved aortic compliance and increased plaque stability. In addition, DHC attenuated systemic and vascular inflammation in ApoE-/- mice. As macrophage inflammation plays an essential role in the pathogenesis of atherosclerosis, we next examined the direct effects of DHC on bone marrow-derived macrophages (BMDMs) in vitro. Our RNA-seq data revealed that DHC dramatically decreased the levels of proinflammatory gene clusters. We verified that DHC significantly downregulated proinflammatory interleukin (IL)-1ß and IL-18 mRNA levels in a time- and concentration-dependent manner. Furthermore, DHC decreased lipopolysaccharide (LPS)-induced inflammation in BMDMs, as evidenced by the reduced protein levels of CD80, iNOS, NLRP3, IL-1ß, and IL-18. Importantly, DHC attenuated LPS-induced activation of p65 and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Thus, we conclude that DHC ameliorates atherosclerosis in ApoE-/- mice by inhibiting inflammation, likely by targeting macrophage p65- and ERK1/2-mediated pathways.

Bromodomain-containing protein 4 and its role in cardiovascular diseases.

Bromodomain-containing protein 4 (BRD4), a chromatin-binding protein, is involved in the development of various tumors. Recent evidence suggests that BRD4 also plays a significant role in cardiovascular diseases, such as ischemic heart disease, hypertension, and cardiac hypertrophy. This review summarizes the roles of BRD4 as a potential regulator of various pathophysiological processes in cardiovascular diseases, implicating that BRD4 may be a new therapeutic target for cardiovascular diseases in the future.

Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall.

Proprotein convertase subtilisin/kexin type-9 (PCSK9), a member of the proprotein convertase family, is an important drug target because of its crucial role in lipid metabolism. Emerging evidence suggests a direct role of localized PCSK9 in the pathogenesis of vascular diseases. With this in our consideration, we reviewed PCSK9 physiology with respect to recent development and major studies (clinical and experimental) on PCSK9 functionality in vascular disease. PCSK9 upregulates low-density lipoprotein (LDL)-cholesterol levels by binding to the LDL-receptor (LDLR) and facilitating its lysosomal degradation. PCSK9 gain-of-function mutations have been confirmed as a novel genetic mechanism for familial hypercholesterolemia. Elevated serum PCSK9 levels in patients with vascular diseases may contribute to coronary artery disease, atherosclerosis, cerebrovascular diseases, vasculitis, aortic diseases, and arterial aging pathogenesis. Experimental models of atherosclerosis, arterial aneurysm, and coronary or carotid artery ligation also support PCSK9 contribution to inflammatory response and disease progression, through LDLR-dependent or -independent mechanisms. More recently, several clinical trials have confirmed that anti-PCSK9 monoclonal antibodies can reduce systemic LDL levels, total nonfatal cardiovascular events, and all-cause mortality. Interaction of PCSK9 with other receptor proteins (LDLR-related proteins, cluster of differentiation family members, epithelial Na+ channels, and sortilin) may underlie its roles in vascular disease. Improved understanding of PCSK9 roles and molecular mechanisms in various vascular diseases will facilitate advances in lipid-lowering therapy and disease prevention.

PCSK9: Associated with cardiac diseases and their risk factors?

PCSK9 plays a critical role in cholesterol metabolism via the PCSK9-LDLR axis. Liver-derived, circulating PCSK9 has become a novel drug target in lipid-lowering therapy. Accumulative evidence supports the possible association between PCSK9 and cardiac diseases and their risk factors. PCSK9 exerts various effects in the heart independently of LDL-cholesterol regulation. Acute myocardial infarction (AMI) induces local and systemic inflammation and reactive oxygen species generation, resulting in increased PCSK9 expression in hepatocytes and cardiomyocytes. PCSK9 upregulation promotes excessive autophagy and apoptosis in cardiomyocytes, thereby contributing to cardiac insufficiency. PCSK9 might also participate in the pathophysiology of heart failure by regulating fatty acid metabolism and cardiomyocyte contractility. It also promotes platelet activation and coagulation in patients with atrial fibrillation. PCSK9 is an independent predictor of aortic valve calcification and accelerates calcific aortic valve disease by regulating lipoprotein(a) catabolism. Accordingly, the use of PCSK9 inhibitors significantly reduced infarct sizes and arrhythmia and improves cardiac contractile function in a rat model of AMI. Circulating PCSK9 levels are positively correlated with age, diabetes mellitus, obesity, and hypertension. Here, we reviewed recent clinical and experimental studies exploring the association between PCSK9, cardiac diseases, and their related risk factors and aiming to identify possible underlying mechanisms.

Curcumin Acetylsalicylate Extends the Lifespan of Caenorhabditis elegans.

Aspirin and curcumin have been reported to be beneficial to anti-aging in a variety of biological models. Here, we synthesized a novel compound, curcumin acetylsalicylate (CA), by combining aspirin and curcumin. We characterized how CA affects the lifespan of Caenorhabditis elegans (C. elegans) worms. Our results demonstrated that CA extended the lifespan of worms in a dose-dependent manner and reached its highest anti-aging effect at the concentration of 20 µM. In addition, CA reduced the deposition of lipofuscin or "age pigment" without affecting the reproductivity of worms. CA also caused a rightward shift of C. elegans lifespan curves in the presence of paraquat-induced (5 mM) oxidative stress or 37 °C acute heat shock. Additionally, CA treatment decreased the reactive oxygen species (ROS) level in C. elegans and increased the expression of downstream genes superoxide dismutase (sod)-3, glutathione S-transferase (gst)-4, heat shock protein (hsp)-16.2, and catalase-1 (ctl-1). Notably, CA treatment resulted in nuclear translocation of the DAF-16 transcription factor, which is known to stimulate the expression of SOD-3, GST-4, HSP-16, and CTL-1. CA did not produce a longevity effect in daf-16 mutants. In sum, our data indicate that CA delayed the aging of C. elegans without affecting reproductivity, and this effect may be mediated by its activation of DAF-16 and subsequent expression of antioxidative genes, such as sod-3 and gst-4. Our study suggests that novel anti-aging drugs may be developed by combining two individual drugs.

Long non-coding RNA H19 in atherosclerosis: what role?

Atherosclerosis (AS) is widely accepted to be a multistep pathophysiological process associated with several other processes such as angiogenesis and inflammatory response. Long non-coding RNAs (lncRNAs) are non-protein coding RNAs (more than 200 nucleotides in length) and can regulate gene expression at the transcriptional and post-transcriptional levels. Recent studies suggest that lncRNA-H19 plays important roles in the regulation of angiogenesis, adipocyte differentiation, lipid metabolism, inflammatory response, cellular proliferation and apoptosis. In this review, we primarily discuss the roles of lncRNA-H19 in atherosclerosis-related pathophysiological processes and the potential mechanisms by which lncRNA-H19 regulates the development of atherosclerosis, to help provide a better understanding of the biological functions of lncRNA-H19 in atherosclerosis.

The Long Noncoding RNA Metastasis-Associated Lung Adenocarcinoma Transcript-1 Regulates CCDC80 Expression by Targeting miR-141-3p/miR-200a-3p in Vascular Smooth Muscle Cells.

OBJECTIVE: Our previous study showed that Coiled-Coil Domain Containing 80 (CCDC80) accelerates the development of atherosclerosis by decreasing lipoprotein lipase (LPL) expression and activity in apoE knockout mice. However, the regulatory mechanism for CCDC80 expression is unclear. This study was designed to evaluate whether noncoding RNAs involved the regulation of CCDC80 expression in vascular smooth muscle cells. METHODS AND RESULTS: Bioinformatics prediction and luciferase reporter gene results showed that miR-141-3p/200a-3p bound to the 3'UTR of CCDC80. Furthermore, miR-141-3p/200a-3p mimics decreased the expression of CCDC80 but increased LPL expression. Opposite results were observed with miR-141-3p/200a-3p inhibitors. We also found that lncRNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) interacted with the sequences of miR-141-3p/200a-3p and decreased their expression. RT-qPCR and western blotting results showed that MALAT1 overexpression increased CCDC80 expression and decreased LPL expression, while MALAT1 knockdown displayed an opposite phenotype. The effects of both MALAT1 overexpression and knockdown were blocked by miR-141-3p/200a-3p mimics or inhibitors. CONCLUSIONS: Thus, we demonstrated that lncRNA MALAT1 regulates CCDC80 and LPL expression through miR-141-3p/200a-3p.

Novel role of the clustered miR-23b-3p and miR-27b-3p in enhanced expression of fibrosis-associated genes by targeting TGFBR3 in atrial fibroblasts.

Atrial fibrillation (AF) is the most common type of arrhythmia in cardiovascular diseases. Atrial fibrosis is an important pathophysiological contributor to AF. This study aimed to investigate the role of the clustered miR-23b-3p and miR-27b-3p in atrial fibrosis. Human atrial fibroblasts (HAFs) were isolated from atrial appendage tissue of patients with sinus rhythm. A cell model of atrial fibrosis was achieved in Ang-II-induced HAFs. Cell proliferation and migration were detected. We found that miR-23b-3p and miR-27b-3p were markedly increased in atrial appendage tissues of AF patients and in Ang-II-treated HAFs. Overexpression of miR-23b-3p and miR-27b-3p enhanced the expression of collagen, type I, alpha 1 (COL1A1), COL3A1 and ACTA2 in HAFs without significant effects on their proliferation and migration. Luciferase assay showed that miR-23b-3p and miR-27b-3p targeted two different sites in 3'-UTR of transforming growth factor (TGF)-ß1 receptor 3 (TGFBR3) respectively. Consistently, TGFBR3 siRNA could increase fibrosis-related genes expression, along with the Smad1 inactivation and Smad3 activation in HAFs. Additionally, overexpression of TGFBR3 could alleviate the increase of COL1A1, COL3A1 and ACTA2 in HAFs after transfection with miR-23b-3p and miR-27b-3p respectively. Moreover, Smad3 was activated in HAFs in response to Ang-II treatment and inactivation of Smad3 attenuated up-regulation of miR-23b-3p and miR-27b-3p in Ang-II-treated HAFs. Taken together, these results suggest that the clustered miR-23b-3p and miR-27b-3p consistently promote atrial fibrosis by targeting TGFBR3 to activate Smad3 signalling in HAFs, suggesting that miR-23b-3p and miR-27b-3p are potential therapeutic targets for atrial fibrosis.

PCSK9: A novel inflammation modulator in atherosclerosis?

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the secretory serine protease family. It binds to low-density lipoprotein receptor (LDLR) for endocytosis and lysosome degradation in the liver, resulting in an increasing in circulating LDL-cholesterol (LDL-c) level. Since a PCSK9 induced increase in plasma LDL-c contributes to atherosclerosis, PCSK9 inhibition has become a new strategy in preventing and treating atherosclerosis. However, in addition to the effect of PCSK9 on elevating blood LDL-c levels, accumulating evidence shows that PCSK9 plays an important role in inflammation, likely representing another major mechanism for PCSK9 to promote atherosclerosis. In this review, we discuss the association of PCSK9 and inflammation, and highlight the specific effects of PCSK9 on different vascular cellular components involved in the atherosclerotic inflammation. We also discuss the clinical evidence for the association between PCSK9 and inflammation in atherosclerotic cardiovascular disease. A better understanding of the direct association of PCSK9 with atherosclerotic inflammation might help establish a new role for PCSK9 in vascular biology and identify a novel molecular mechanism for PCSK9 therapy.

Nobiletin reduces LPL-mediated lipid accumulation and pro-inflammatory cytokine secretion through upregulation of miR-590 expression.

Nobiletin has protective effects on cardiovascular diseases, but the mechanism is not clear. In this study, we examined whether nobiletin affects the expression of miR-590/LPL and its relative effects on lipid accumulation and pro-inflammatory cytokine secretion in human THP-1 macrophages. RT-qPCR analysis showed that nobiletin increased the expression of miR-590. Western blot analysis showed that nobiletin-suppressed LPL expression was enhanced by miR-590 mimic and abrogated by miR-590 inhibitor. Oil Red O staining and high-performance liquid chromatography assays showed that nobiletin attenuated lipid accumulation in macrophages. Treatment with nobiletin and miR-590 mimic decreased cellular lipid accumulation, whereas treatment with miR-590 inhibitor increased cellular lipid accumulation. ELISA illustrated that nobiletin alleviated pro-inflammatory cytokine secretion in macrophages as measured by, which was reduced by miR-590 mimic and increased by miR-590 inhibitor. In conclusion, nobiletin may alleviate lipid accumulation and secretion of pro-inflammatory cytokines by enhancing the inhibitory effect of miR-590 on LPL expression, suggesting a promising strategy for potential drug development for atherosclerosis.

Itaconate: an emerging determinant of inflammation in activated macrophages.

Macrophages play a central role in innate immunity as the first line of defense against pathogen infection. Upon exposure to inflammatory stimuli, macrophages rapidly respond and subsequently undergo metabolic reprogramming to substantially produce cellular metabolites such as itaconate. As a derivate of the tricarboxylic acid cycle, itaconate is derived from the decarboxylation of cis-aconitate mediated by immunoresponsive gene 1 in the mitochondrial matrix. It is well known that itaconate has a direct antimicrobial effect by inhibiting isocitrate lyase. Strikingly, two recent studies published in Nature showed that itaconate markedly decreases the production of proinflammatory mediators in lipopolysaccharide-treated macrophages and ameliorates sepsis and psoriasis in animal models, revealing a novel biological action of itaconate beyond its regular roles in antimicrobial defense. The mechanism for this anti-inflammatory effect has been proposed to involve the inhibition of succinate dehydrogenase, blockade of IκBζ translation and activation of Nrf2. These intriguing discoveries provide a new explanation for how macrophages are switched from a pro- to an anti-inflammatory state to limit the damage and facilitate tissue repair under proinflammatory conditions. Thus, the emerging effect of itaconate as a crucial determinant of macrophage inflammation has important implications in further understanding cellular immunometabolism and developing future therapeutics for the treatment of inflammatory diseases. In this review, we focus on the roles of itaconate in controlling the inflammatory response during macrophage activation, providing a rationale for future investigation and therapeutic intervention.

IL-8 negatively regulates ABCA1 expression and cholesterol efflux via upregulating miR-183 in THP-1 macrophage-derived foam cells.

OBJECTIVE: Previous studies suggest that IL-8 has an important role in the regulation of cholesterol efflux, but whether miRNAs are involved in this process is still unknown. The purpose of this study is to explore whether IL-8 promotes cholesterol accumulation by enhancing miR-183 expression in macrophages and its underlying mechanism. METHODS AND RESULTS: Treatment of THP-1 macrophage-derived foam cells with IL-8 decreased ABCA1 expression and cholesterol efflux. Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-183 was highly conserved during evolution and directly inhibited ABCA1 protein and mRNA expression by targeting ABCA1 3'UTR. MiR-183 directly regulated endogenous ABCA1 expression levels. Furthermore, IL-8 enhanced the expression of miR-183 and decrease ABCA1 expression. Cholesterol transport assays confirmed that IL-8 dramatically inhibited apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux by increasing miR-183 expression. In contrast, treatment with anti-IL-8 antibody reversed these effects. CONCLUSION: IL-8 enhances the expression of miR-183, which then inhibits ABCA1 expression and cholesterol efflux. Our studies suggest that the IL-8-miR-183-ABCA1 axis may play an intermediary role in the development of atherosclerosis.

Pregnancy-Associated Plasma Protein-A Accelerates Atherosclerosis by Regulating Reverse Cholesterol Transport and Inflammation.

BACKGROUND: Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis. Methods and Results: PAPP-A was silenced in apolipoprotein E (apoE-/-) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE-/-mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE-/-mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1ß through the nuclear factor kappa-B (NF-κB) pathway. CONCLUSIONS: The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE-/-mice through reducing RCT capacity and activating an inflammatory response.

[Identification of 23 unknown Li minority medicinal plants based on DNA barcoding].

DNA barcode molecular biological technique is used to identify the species of 23 unknown Li minority medicinal plants.DNA was extracted from 23 unknown medicines using the Plant Genomic DNA Extraction kit. The ITS2 and psbA-trnH regions were amplified and sequenced bi-directionally. The Codon Code Aligner V 7. 0. 1 was used to proofread and assemble the contigs and generated consensus sequences. All the sequences were submitted to Traditional Chinese Medicine DNA Barcode Database and NCBI Gen Bank to get information of the species identifications. If the maximum similarity of the identification result is ≥ 97%,exact species can be known. If it is between 97% and 90%,samples' genus can be confirmed; If it is <90%,then we can only confirm its family. Finally there are 17 samples can be identified to species level,5 can be identified to genus level and 1 can be identified to family level. This shows that DNA barcoding used in medicinal plants molecular identification,can identify unknown species rapidly and accurately.

MicroRNA-296: a promising target in the pathogenesis of atherosclerosis?

Atherosclerosis has been recognized as an inflammatory disease involving the vascular wall. MicroRNAs are a group of small noncoding RNAs to regulate gene expression at the transcriptional level through mRNA degradation or translation repression. Recent studies suggest that miR-296 may play crucial roles in the regulation of angiogenesis, inflammatory response, cholesterol metabolism, hypertension, cellular proliferation and apoptosis. In this review, we primarily discussed the molecular targets of miR-296 involved in the development of atherosclerosis, which may provide a basis for future investigation and a better understanding of the biological functions of miR-296 in atherosclerosis.

Visceral adipose tissue-derived serine protease inhibitor accelerates cholesterol efflux by up-regulating ABCA1 expression via the NF-κB/miR-33a pathway in THP-1 macropahge-derived foam cells.

Atherosclerosis is a dyslipidemia disease characterized by foam cell formation driven by the accumulation of lipids. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is known to suppress the development of atherosclerosis via its anti-inflammatory properties, but it is not yet known whether vaspin affects cholesterol efflux in THP-1 macrophage-derived foam cells. Here, we investigated the effects of vaspin on ABCA1 expression and cholesterol efflux, and further explored the underlying mechanism. We found that vaspin decreased miR-33a levels, which in turn increased ABCA1 expression and cholesteorl efflux. We also found that inhibition of NF-κB reduced miR-33a expression and vaspin suppressed LPS-mediated NF-κB phosphorylation. Our findings suggest that vaspin is not only a regular of inflammasion but also a promoter of cholesterol efflux.